Alan K Percy, Jeffrey L Neul, Timothy A Benke, Elizabeth M Berry-Kravis, Daniel G Glaze, Eric D Marsh, Di An, Kathie M Bishop, James M Youakim
{"title":"曲非奈德治疗雷特综合征:开放标签扩展 LILAC 研究的结果。","authors":"Alan K Percy, Jeffrey L Neul, Timothy A Benke, Elizabeth M Berry-Kravis, Daniel G Glaze, Eric D Marsh, Di An, Kathie M Bishop, James M Youakim","doi":"10.1016/j.medj.2024.05.018","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Trofinetide was approved for the treatment of Rett syndrome based on the results of the phase 3, randomized, placebo-controlled, 12-week LAVENDER study. Rett syndrome is a chronic disorder requiring long-term treatment. We report the efficacy and safety results of LILAC, a 40-week, open-label extension study of LAVENDER.</p><p><strong>Methods: </strong>Females with Rett syndrome aged 5-21 years received open-label treatment with trofinetide for 40 weeks. The primary endpoint was long-term safety of trofinetide; secondary endpoints included the change from baseline at week 40 in the Rett Syndrome Behaviour Questionnaire score and the Clinical Global Impression-Improvement score at week 40.</p><p><strong>Findings: </strong>Overall, 154 participants were enrolled and treated with trofinetide in LILAC. The most common adverse events in LILAC were diarrhea (74.7%), vomiting (28.6%), and COVID-19 (11.0%). Diarrhea was the most common adverse event leading to treatment withdrawal (21.4%). The Rett Syndrome Behaviour Questionnaire mean score (standard error) improvement from the LAVENDER baseline to week 40 in LILAC was -7.3 (1.62) and -7.0 (1.61) for participants treated with trofinetide and placebo in LAVENDER, respectively. Mean Clinical Global Impression-Improvement scores (standard error) at week 40 rated from the LILAC baseline were 3.1 (0.11) and 3.2 (0.14) for participants treated with trofinetide and placebo in LAVENDER, respectively.</p><p><strong>Conclusions: </strong>Treatment with trofinetide for ≤40 weeks continued to improve symptoms of Rett syndrome. Trofinetide had a similar safety profile in LILAC as in LAVENDER.</p><p><strong>Funding: </strong>The study was supported by Acadia Pharmaceuticals Inc. (San Diego, CA, USA). This trial was registered at ClinicalTrials.gov (NCT04279314).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1178-1189.e3"},"PeriodicalIF":12.8000,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study.\",\"authors\":\"Alan K Percy, Jeffrey L Neul, Timothy A Benke, Elizabeth M Berry-Kravis, Daniel G Glaze, Eric D Marsh, Di An, Kathie M Bishop, James M Youakim\",\"doi\":\"10.1016/j.medj.2024.05.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Trofinetide was approved for the treatment of Rett syndrome based on the results of the phase 3, randomized, placebo-controlled, 12-week LAVENDER study. Rett syndrome is a chronic disorder requiring long-term treatment. We report the efficacy and safety results of LILAC, a 40-week, open-label extension study of LAVENDER.</p><p><strong>Methods: </strong>Females with Rett syndrome aged 5-21 years received open-label treatment with trofinetide for 40 weeks. The primary endpoint was long-term safety of trofinetide; secondary endpoints included the change from baseline at week 40 in the Rett Syndrome Behaviour Questionnaire score and the Clinical Global Impression-Improvement score at week 40.</p><p><strong>Findings: </strong>Overall, 154 participants were enrolled and treated with trofinetide in LILAC. The most common adverse events in LILAC were diarrhea (74.7%), vomiting (28.6%), and COVID-19 (11.0%). Diarrhea was the most common adverse event leading to treatment withdrawal (21.4%). The Rett Syndrome Behaviour Questionnaire mean score (standard error) improvement from the LAVENDER baseline to week 40 in LILAC was -7.3 (1.62) and -7.0 (1.61) for participants treated with trofinetide and placebo in LAVENDER, respectively. Mean Clinical Global Impression-Improvement scores (standard error) at week 40 rated from the LILAC baseline were 3.1 (0.11) and 3.2 (0.14) for participants treated with trofinetide and placebo in LAVENDER, respectively.</p><p><strong>Conclusions: </strong>Treatment with trofinetide for ≤40 weeks continued to improve symptoms of Rett syndrome. Trofinetide had a similar safety profile in LILAC as in LAVENDER.</p><p><strong>Funding: </strong>The study was supported by Acadia Pharmaceuticals Inc. (San Diego, CA, USA). 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Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study.
Background: Trofinetide was approved for the treatment of Rett syndrome based on the results of the phase 3, randomized, placebo-controlled, 12-week LAVENDER study. Rett syndrome is a chronic disorder requiring long-term treatment. We report the efficacy and safety results of LILAC, a 40-week, open-label extension study of LAVENDER.
Methods: Females with Rett syndrome aged 5-21 years received open-label treatment with trofinetide for 40 weeks. The primary endpoint was long-term safety of trofinetide; secondary endpoints included the change from baseline at week 40 in the Rett Syndrome Behaviour Questionnaire score and the Clinical Global Impression-Improvement score at week 40.
Findings: Overall, 154 participants were enrolled and treated with trofinetide in LILAC. The most common adverse events in LILAC were diarrhea (74.7%), vomiting (28.6%), and COVID-19 (11.0%). Diarrhea was the most common adverse event leading to treatment withdrawal (21.4%). The Rett Syndrome Behaviour Questionnaire mean score (standard error) improvement from the LAVENDER baseline to week 40 in LILAC was -7.3 (1.62) and -7.0 (1.61) for participants treated with trofinetide and placebo in LAVENDER, respectively. Mean Clinical Global Impression-Improvement scores (standard error) at week 40 rated from the LILAC baseline were 3.1 (0.11) and 3.2 (0.14) for participants treated with trofinetide and placebo in LAVENDER, respectively.
Conclusions: Treatment with trofinetide for ≤40 weeks continued to improve symptoms of Rett syndrome. Trofinetide had a similar safety profile in LILAC as in LAVENDER.
Funding: The study was supported by Acadia Pharmaceuticals Inc. (San Diego, CA, USA). This trial was registered at ClinicalTrials.gov (NCT04279314).
期刊介绍:
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